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Upregulation of p16(INK4A) and Bax in p53 wild/p53-overexpressing crypts in ulcerative colitis-associated tumours.

Yoshida T, Matsumoto N, Mikami T, Okayasu I - Br. J. Cancer (2004)

Bottom Line: In ulcerative colitis (UC)-associated tumours, p53 gene mutations and p53 protein overexpression are frequently found in early stages, but the two types of alteration do not always coincide.Regarding these mismatched crypts of the first type, significant increase in p16(INK4A) and Bax expression was found.No significant relation with p53-related gene products was detected with the p53 protein overexpression (-)/p53 mutation (+) mismatch.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. tyoshida@med.kitasato-u.ac.jp

ABSTRACT
In ulcerative colitis (UC)-associated tumours, p53 gene mutations and p53 protein overexpression are frequently found in early stages, but the two types of alteration do not always coincide. To clarify this discrepancy, p53 mutations and expression of p53-associated molecules were analysed in UC-associated dysplasias by a combination of microdissection, polymerase chain reaction-direct sequencing and immunohistochemistry at the single crypt level. Mismatch of p53 protein overexpression (+)/mutation (-) or p53 overexpression (-)/gene mutation (+) was found in nine crypts in regenerative mucosa (19 crypts), in 27 in low-grade dysplasia (41), in one in high-grade dysplasia (5) and in 12 in invasive carcinomas (17). Regarding these mismatched crypts of the first type, significant increase in p16(INK4A) and Bax expression was found. The Ki-67 labelling index was depressed in such p53-diffusely positive lesions with the wild-type p53 gene, compared to their p53-diffusely positive and mutant type counterparts. p16(INK4A) was upregulated indirectly as part of the negative feedback, and increase in Bax, directly controlled by wild-type p53, indicates upregulation of apoptosis. No significant relation with p53-related gene products was detected with the p53 protein overexpression (-)/p53 mutation (+) mismatch. Therefore, a tumorigenesis pathway independent of p53 dysfunction appears to exist in association with ulcerative colitis.

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Related in: MedlinePlus

Immunopositivity of p53-related molecules compared to p53 overexpression in UC-associated dysplastic lesions and regenerative crypts. Percentages or scores for immunopositivity are shown as in Figure 2. A: p21Cip1, B: p27Kip1, C: p16INK4A, D: p14ARF, E: Mdm2, F: Bax and G: Ki-67. Degrees of p53 overexpression are shown as −, +/−, + and ++, as described in Materials and methods. (a) P<0.01; (b) P<0.05 by Fisher's PLSD test.
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fig4: Immunopositivity of p53-related molecules compared to p53 overexpression in UC-associated dysplastic lesions and regenerative crypts. Percentages or scores for immunopositivity are shown as in Figure 2. A: p21Cip1, B: p27Kip1, C: p16INK4A, D: p14ARF, E: Mdm2, F: Bax and G: Ki-67. Degrees of p53 overexpression are shown as −, +/−, + and ++, as described in Materials and methods. (a) P<0.01; (b) P<0.05 by Fisher's PLSD test.

Mentions: REG=regenerative epithelium; LGD=low-grade dysplasia; HGD=high-grade dysplasia; UC=ulcerative colitis; Inv. Ca.=invasive carcinoma.


Upregulation of p16(INK4A) and Bax in p53 wild/p53-overexpressing crypts in ulcerative colitis-associated tumours.

Yoshida T, Matsumoto N, Mikami T, Okayasu I - Br. J. Cancer (2004)

Immunopositivity of p53-related molecules compared to p53 overexpression in UC-associated dysplastic lesions and regenerative crypts. Percentages or scores for immunopositivity are shown as in Figure 2. A: p21Cip1, B: p27Kip1, C: p16INK4A, D: p14ARF, E: Mdm2, F: Bax and G: Ki-67. Degrees of p53 overexpression are shown as −, +/−, + and ++, as described in Materials and methods. (a) P<0.01; (b) P<0.05 by Fisher's PLSD test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747701&req=5

fig4: Immunopositivity of p53-related molecules compared to p53 overexpression in UC-associated dysplastic lesions and regenerative crypts. Percentages or scores for immunopositivity are shown as in Figure 2. A: p21Cip1, B: p27Kip1, C: p16INK4A, D: p14ARF, E: Mdm2, F: Bax and G: Ki-67. Degrees of p53 overexpression are shown as −, +/−, + and ++, as described in Materials and methods. (a) P<0.01; (b) P<0.05 by Fisher's PLSD test.
Mentions: REG=regenerative epithelium; LGD=low-grade dysplasia; HGD=high-grade dysplasia; UC=ulcerative colitis; Inv. Ca.=invasive carcinoma.

Bottom Line: In ulcerative colitis (UC)-associated tumours, p53 gene mutations and p53 protein overexpression are frequently found in early stages, but the two types of alteration do not always coincide.Regarding these mismatched crypts of the first type, significant increase in p16(INK4A) and Bax expression was found.No significant relation with p53-related gene products was detected with the p53 protein overexpression (-)/p53 mutation (+) mismatch.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. tyoshida@med.kitasato-u.ac.jp

ABSTRACT
In ulcerative colitis (UC)-associated tumours, p53 gene mutations and p53 protein overexpression are frequently found in early stages, but the two types of alteration do not always coincide. To clarify this discrepancy, p53 mutations and expression of p53-associated molecules were analysed in UC-associated dysplasias by a combination of microdissection, polymerase chain reaction-direct sequencing and immunohistochemistry at the single crypt level. Mismatch of p53 protein overexpression (+)/mutation (-) or p53 overexpression (-)/gene mutation (+) was found in nine crypts in regenerative mucosa (19 crypts), in 27 in low-grade dysplasia (41), in one in high-grade dysplasia (5) and in 12 in invasive carcinomas (17). Regarding these mismatched crypts of the first type, significant increase in p16(INK4A) and Bax expression was found. The Ki-67 labelling index was depressed in such p53-diffusely positive lesions with the wild-type p53 gene, compared to their p53-diffusely positive and mutant type counterparts. p16(INK4A) was upregulated indirectly as part of the negative feedback, and increase in Bax, directly controlled by wild-type p53, indicates upregulation of apoptosis. No significant relation with p53-related gene products was detected with the p53 protein overexpression (-)/p53 mutation (+) mismatch. Therefore, a tumorigenesis pathway independent of p53 dysfunction appears to exist in association with ulcerative colitis.

Show MeSH
Related in: MedlinePlus